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Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in...
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Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 15122

Special Issue Editor

Dr. Nuno Vale

E-Mail Website
Guest Editor
Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Interests: drug permeability; biomimetic membranes; transporters/efflux; organ-on-chip; IVIVE; PBPK/QSP; drug combinations/polypharmacy; DDIs; AI/ML prediction; digital twins; precision dosing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advancements in molecular precision therapeutics have revolutionized the understanding and treatment of complex diseases. This special issue aims to unravel novel mechanisms and delivery strategies at the molecular level, fostering interdisciplinary research efforts. With the rapid progress in genomics, proteomics, and advanced drug delivery systems, we seek to explore precision medicine's frontiers in diagnosing, targeting, and treating diseases with unparalleled specificity and efficacy. Key topics encompass the identification of disease biomarkers, development of novel therapeutic molecules, and innovative delivery approaches for enhanced patient outcomes. Recent trends emphasize the integration of bioinformatics, nanotechnology, and synthetic biology to design personalized therapies. This call for papers invites contributions that showcase the latest research advancements, challenges, and future directions in this rapidly evolving field.

Dr. Nuno Vale
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular precision therapeutics
  • disease biomarkers
  • novel therapeutic molecules
  • drug delivery strategies
  • personalized medicine
  • bioinformatics
  • nanotechnology
  • synthetic biology

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Published Papers (5 papers)

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Editorial

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4 pages, 171 KB  
Editorial
Special Issue “Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases”
by Nuno Vale
Int. J. Mol. Sci. 2025, 26(15), 7439; https://doi.org/10.3390/ijms26157439 - 1 Aug 2025
Viewed by 846
Abstract
In recent years, advancements in molecular precision therapeutics have profoundly reshaped the understanding and treatment of complex diseases [...] Full article
(This article belongs to the Special Issue Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases)

Research

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20 pages, 6310 KB  
Article
Consensus Copy-Number Alteration Signatures from Clinical Panels Enable Pan-Cancer Risk Stratification and Therapy Response Association
by Adar Yaacov
Int. J. Mol. Sci. 2026, 27(4), 1764; https://doi.org/10.3390/ijms27041764 - 12 Feb 2026
Viewed by 437
Abstract
Somatic copy-number alterations (CNAs) are pervasive in cancer, but routine targeted panels yield sparse CNA readouts unsuited for CNA signature analysis. We built a consensus framework that integrates four deconvolution algorithms to extract CNA signatures from panel data. Analysis of 24,870 tumors sequenced [...] Read more.
Somatic copy-number alterations (CNAs) are pervasive in cancer, but routine targeted panels yield sparse CNA readouts unsuited for CNA signature analysis. We built a consensus framework that integrates four deconvolution algorithms to extract CNA signatures from panel data. Analysis of 24,870 tumors sequenced using MSK-IMPACT identified five reproducible signatures (CON1–CON5). CON5 mirrored near-diploid profiles, whereas the others captured distinct aneuploid patterns. Technical fidelity was confirmed by internal cross-validation and external validation in sarcoma and hepatocellular carcinoma cohorts. Clinically, these signatures were associated with overall survival across tumor types (hazard ratio 1.3–2.5; FDR < 0.01) and provided additive prognostic information beyond Fraction of Genome Altered. Associations with driver mutations (GATA3 in CON1, KRAS in CON5) supported biological specificity, and the signatures delineated resistance landscapes for chemotherapy, hormonal, targeted, and immunotherapy. By converting routine panel data into biologically interpretable prognostic features, our framework enables risk stratification and therapeutic guidance in precision oncology. Full article
(This article belongs to the Special Issue Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases)
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Graphical abstract

14 pages, 2222 KB  
Article
BRAF V600E Mutation Has Variable Tumor-Specific Effects on Expression of MAPK Pathway Genes That Could Affect Patient Outcome
by Sourat Darabi, Phillip Stafford, David R. Braxton, Carlos E. Zuazo, Taylor J. Brodie and Michael J. Demeure
Int. J. Mol. Sci. 2025, 26(16), 7910; https://doi.org/10.3390/ijms26167910 - 16 Aug 2025
Cited by 5 | Viewed by 2868
Abstract
BRAF inhibitors have a 50–70% response rate in melanoma but are less effective for thyroid cancer. Differential response may be from activation or expression of downstream mitogen-activated protein kinase (MAPK) pathway genes. Retrospective analysis compared whole exome and transcriptome sequencing in melanoma and [...] Read more.
BRAF inhibitors have a 50–70% response rate in melanoma but are less effective for thyroid cancer. Differential response may be from activation or expression of downstream mitogen-activated protein kinase (MAPK) pathway genes. Retrospective analysis compared whole exome and transcriptome sequencing in melanoma and thyroid cancers from April 2019 to October 2023. The MAPK Activation Score (MPAS) was calculated using Z-score normalized/log-transformed values indicating expression across 10 MAPK-associated genes. Our tumor registry provided outcome data. BRAF V600E mutations were identified in 33 of 200 (17%) melanomas and 14 (7%) had other BRAF mutations (V600K/R). Of 49 thyroid tumor samples, BRAF V600E mutations were found in 19 (39%). RNA expression of BRAF and the 10 MAPK-associated genes were increased in melanomas with V600E compared to wild-type BRAF (p = 0.02). Conversely, BRAF V600E mutation in thyroid cancer was not associated with increased expression nor MAPK pathway activation. No significant difference in overall survival based on BRAF mutation was observed in the subset of patients where data was available. The MAPK pathway is differentially affected by the different cancers, with increased MAPK activation observed in melanoma and not in thyroid cancer. This may account in part for the observed differential response to BRAF inhibitors. Full article
(This article belongs to the Special Issue Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases)
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39 pages, 11985 KB  
Article
Molecular Precision Medicine: Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug–Drug Interactions Between Lidocaine and Rocuronium/Propofol/Paracetamol
by Abigail Silva, Joana Mourão and Nuno Vale
Int. J. Mol. Sci. 2025, 26(4), 1506; https://doi.org/10.3390/ijms26041506 - 11 Feb 2025
Cited by 1 | Viewed by 4606
Abstract
The perioperative period, encompassing preoperative, intraoperative, and postoperative phases, is crucial for comprehensive patient care. During this time, the use of opioids and other drugs can lead to drug–drug interactions (DDIs), potentially resulting in adverse drug reactions (ADRs) that increase morbidity, mortality, and [...] Read more.
The perioperative period, encompassing preoperative, intraoperative, and postoperative phases, is crucial for comprehensive patient care. During this time, the use of opioids and other drugs can lead to drug–drug interactions (DDIs), potentially resulting in adverse drug reactions (ADRs) that increase morbidity, mortality, and healthcare costs. This study investigates the drug–drug interactions (DDIs) between rocuronium, propofol, paracetamol, and lidocaine, focusing on the CYP-mediated metabolism of these drugs in the perioperative context, where these drugs are frequently co-administered. Using physiologically based pharmacokinetic (PBPK) modeling through the GastroPlus™ software and in vitro experiments with Hep G2 cells, we aimed to assess potential toxicities and pharmacokinetic interactions. Cellular viability assays revealed significant toxicity when lidocaine was combined with propofol and rocuronium, while paracetamol exhibited no considerable impact on viability. PBPK simulations confirmed moderate interactions with rocuronium and weak interactions with propofol but no relevant interactions with paracetamol. These findings emphasize the need for dose adjustments in perioperative settings to enhance patient safety, particularly with propofol and rocuronium, while supporting the co-administration of lidocaine and paracetamol. These findings show the importance of moving towards a personalized medicine model, adjusting the clinical use of lidocaine according to individual patient needs, thus promoting safer and more effective perioperative care and moving beyond the “one-size-fits-all” approach in anesthetic management. Full article
(This article belongs to the Special Issue Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases)
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Review

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19 pages, 314 KB  
Review
Current Status of Precision Medicine in Colorectal Cancer in Japan
by Yoshiki Kojitani and Masayuki Takeda
Int. J. Mol. Sci. 2025, 26(11), 5029; https://doi.org/10.3390/ijms26115029 - 23 May 2025
Cited by 3 | Viewed by 5467
Abstract
Colorectal cancer (CRC) remains a major health burden in Japan, with precision medicine playing an increasingly critical role in treatment optimization. Key biomarkers, including RAS, BRAF, microsatellite instability/mismatch repair, and human epidermal growth factor receptor 2, can be used as a [...] Read more.
Colorectal cancer (CRC) remains a major health burden in Japan, with precision medicine playing an increasingly critical role in treatment optimization. Key biomarkers, including RAS, BRAF, microsatellite instability/mismatch repair, and human epidermal growth factor receptor 2, can be used as a guide for molecularly targeted therapies and immunotherapy. Advances in molecular diagnostics, including comprehensive genomic profiling, have enabled more precise treatment selection such as RET and NTRK fusions. Nationwide initiatives, such as c-CAT and SCRUM-Japan, can leverage real-world data to refine clinical strategies. Recent developments in circulating tumor DNA analysis have led to novel approaches for minimal residual disease monitoring, as demonstrated by the CIRCULATE-Japan GALAXY study. However, certain challenges persist, including the time required for genetic testing, the limited availability of targeted therapies, and disparities in access to molecular tumor boards. This review summarizes the current landscape of precision medicine in CRC in Japan, emphasizing key biomarkers, genetic testing strategies, targeted therapies, and emerging technologies. Future research should focus on expanding clinical trial access, accelerating drug approvals, and integrating real-world data into clinical practice to further advance precision medicine. Full article
(This article belongs to the Special Issue Molecular Precision Medicine: Unraveling Novel Mechanisms and Delivery Strategies in Complex Diseases)
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